This Program Project consists of three individual and two core projects. Project 0003 is designed to identify and quantify the interactive factors of mechanical force, electrical stimulation, hormonal and neural influences on motor units and muscles in adult cats. This project will provide an extremely well controlled series of experiments from which the relative importance of three critical variables previously associated with muscle fiber phenotype expression of myosin isoforms can be determined. A detailed examination of the locomotor capacity of spinally transected cats at selected stages of recovery and the response to specific training protocols during recovery will be studied in Project 0009, Project 0009 is also designed to identify neuropharmacological systems which are modulated during recovery from spinalization and to determine the degree to which these modulations are dependent on the type of training. The objective of Project 0010 is to complete a carefully controlled clinical trial to determine the feasibility of entraining neurally-impaired patients to regain significant locomotor capability. The entrainment procedures will consist of stepping on the clinical trial design emphasizes a comprehensive analysis of subject oriented factors related to mobility and quality of life of a small population of subjects, as opposed to a less detailed analysis of a large number of subjects. Two cores provide services for the three individual grants. In Core I, animal and administrative resources are provided. In Core II, a complex array of computer systems are interfaced for maximum utilization of computer resources. Extensive 3-D imaging of anatomical and physiological data will be used. Core II also includes the required statistical expertise. The participants of the grant are from 2 campuses and 2 countries. Within UCLA, five departments are represented. There are 11 scientists participating in the grant activities. The overall objective of this Program Project is to determine the degree of and to identify physiological and molecular mechanisms for inducing neuromuscular plasticity that can occur after spinalization and to define optimal procedures to assure that the plasticity maximizes functional recovery.